Is MYO7A p.Ala1492= (c.4476C>T) pathogenic?

MYO7A p.Ala1492= (c.4476C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-10-07). Very rare (popmax 0.00534%, afr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Ala1492= (c.4476C>T)?

MYO7A p.Ala1492= (c.4476C>T) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Ala1492= (c.4476C>T) in the general population?

MYO7A p.Ala1492= (c.4476C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

MYO7A p.Ala1492=

c.4476C>T · rs777008254 · VCV883826

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -15	GERP -3.5
Overall
CADD	0.848	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,944 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,613,782 alleles · very rare exomes 23/1,461,564 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
European (non-Finnish)	0.00186%	53,631

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7A
Protein: p.Ala1492=
Coding: c.4476C>T
MANE Select: NM_000260
dbSNP: rs777008254
Type: single nucleotide variant
Location: chr11:77198529 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1492: the ferm 1 domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Ala1492Thr Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7a-p-ala1492 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown